<i>Chlamydia pneumoniae</i>
            Stimulates Proliferation of Vascular Smooth Muscle Cells Through Induction of Endogenous Heat Shock Protein 60

Hirono, Shuichi; Dibrov, Elena; Hurtado, Cecilia; Kostenuk, Annette; Ducas, Robin; Pierce, Grant N.

doi:10.1161/01.res.0000095720.46043.f2

Cited by 70 publications

(60 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Differences between treatment groups were assessed by one-way analysis of variance (ANOVA) using the Student-Newman-Keuls method (Hirono et al 2003). A probability of P ≤ 0.05 was considered statistically significant.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Development of a novel rationally designed antibiotic to inhibit a nontraditional bacterial target

Dibrov

Maddaford

et al. 2017

Can. J. Physiol. Pharmacol.

Self Cite

View full text Add to dashboard Cite

Abstract:The search for new nontraditional targets is a high priority in antibiotic design today. Bacterial membrane energetics based on sodium ion circulation offers potential alternative targets. The present work identifies the Na + -translocating NADH: ubiquinone oxidoreductase (Na + -NQR), a key respiratory enzyme in many microbial pathogens, as indispensible for the Chlamydia trachomatis infectious process. Infection by Chlamydia trachomatis significantly increased first H + and then Na + levels within the host mammalian cell. A newly designed furanone Na + -NQR inhibitor, PEG-2S, blocked the changes in both H + and Na + levels induced by Chlamydia trachomatis infection. It also inhibited intracellular proliferation of Chlamydia trachomatis with a half-minimal inhibitory concentration in the submicromolar range but did not affect the viability of mammalian cells or bacterial species representing benign intestinal microflora. At low nanomolar concentrations (IC 50 value = 1.76 nmol/L), PEG-2S inhibited the Na + -NQR activity in sub-bacterial membrane vesicles isolated from Vibrio cholerae. Taken together, these results show, for the first time, that Na + -NQR is critical for the bacterial infectious process and is susceptible to a precisely targeted bactericidal compound in situ. The obtained data have immediate relevance for many different diseases caused by pathogenic bacteria that rely on Na + -NQR activity for growth, including sexually transmitted, pulmonary, oral, gum, and ocular infections.Key words: Na + -translocating NADH:ubiquinone oxidoreductase, Na + -NQR, antibiotic design, Chlamydia, bacteria, infection.Résumé : La recherche de nouvelles cibles non traditionnelles est aujourd'hui une grande priorité du domaine de la conception d'antibiotiques. Les propriétés énergétiques des membranes bactériennes fondées sur le transfert des ions sodiques offrent d'autres choix de cibles potentielles. Les présents travaux traitent de la NADH : ubiquinone oxydoréductase induisant la translocation des ions Na + (Na + -NQR), une enzyme clé de la respiration cellulaire chez beaucoup de microbes pathogènes, comme élément indispensable du processus infectieux associé à Chlamydia trachomatis. L'infection par Chlamydia trachomatis entraînait une augmentation marquée des taux d'ions H + puis d'ions Na + à l'intérieur des cellules de mammifère hôtes. Le PEG-2S, une furanone inhibitrice de la Na + -NQR nouvellement conçue, inhibait la variation des taux d'ions H + comme d'ions Na + induite par l'infection par Chlamydia trachomatis. Il inhibait aussi la prolifération intracellulaire de Chlamydia trachomatis avec une concentration minimale inhibitrice 50 de l'ordre du submicromolaire, mais il n'affectait pas la viabilité des cellules de mammifère ni d'espèces bactériennes représentant la flore microbienne intestinale bénigne. À des concentrations nanomolaires faibles (CI 50 = 1,76 nmol/L), le PEG-2S inhibait l'activité de la Na + -NQR dans les vésicules bactériennes submembrannaires isolées de Vibrio cholerae. Dans l'ense...

show abstract

Section: Discussionmentioning

confidence: 99%

“…Chlamydia trachomatis serovar L 2 was propagated as described previously (Hirono et al 2003). The purified organism was stored in SPG buffer (0.22 mol/L sucrose, 8.6 mmol/L Na 2 HPO 4 , 3.8 mmol/L KH 2 PO 4 , 5 mmol/L glutamic acid, 0.2 m filtered, pH 7.4) at -80°C until use.…”

Section: Bacterial Strains and Cultivationmentioning

confidence: 99%

Development of a novel rationally designed antibiotic to inhibit a nontraditional bacterial target

Dibrov

Maddaford

et al. 2017

Can. J. Physiol. Pharmacol.

Self Cite

View full text Add to dashboard Cite

show abstract

“…This proliferative mechanism may be enhanced by Chlamydia pneumonia infection, which induces endogenous HSP60 overexpression in VSMC [93]. These observations suggest that a timely treatment of infectious diseases may reduce the progression of ATS and related complications.…”

Section: Hsp60 and Its Bacterial Counterpart Are Pro-atherogenic Molementioning

confidence: 90%

Heat Shock Protein-60 and Risk for Cardiovascular Disease

Rizzo¹,

Macario²,

Macario³

et al. 2011

CPD

View full text Add to dashboard Cite

Cardiovascular disease (CVD) is a leading cause of morbidity and mortality worldwide. There is growing evidence that molecular chaperones, many of which are heat shock proteins HSPs, are involved in CVD pathogenesis. In this review we focus on HSP60, the human mitochondrial chaperone that also displays extramitochondrial and extracellular functions. HSP60 is typically cytoprotective but a number of stress conditions determine its conversion to a potentially toxic molecule for cells and tissues. We present illustrative examples of specific subtypes of CVD where HSP60 is implicated in the initiation and/or progression of disease. The data not only indicate a pathogenic role for HSP60 but also its potential as a biomarker with applications for diagnosis, assessing prognosis and response to treatment, as well as for preventing and treating CVD.

show abstract

“…The absence of an effect on cyclin B1 may explain why C. pneumoniae infection does not appear to be associated with a delay in host cell cycle progression (5,28). Rather, evidence points to the tendency of C. pneumoniae infection to actually stimulate vascular proliferation and remodeling (20,37). Perhaps this difference in the effect of C. trachomatis infection and that of C. pneumoniae infection on host cell cycle progression is partially responsible for the disparity in the types of diseases caused by these two organisms.…”

Section: Discussionmentioning

confidence: 99%

Chlamydia trachomatis Infection Induces Cleavage of the Mitotic Cyclin B1

et al. 2006

View full text Add to dashboard Cite

The obligate intracellular pathogen Chlamydia trachomatis interferes with a number of host cell processes, including cytoskeletal organization, vesicular trafficking, and apoptosis. In this study we report that C. trachomatisinfected cells proliferate more slowly than uninfected cells, suggesting that C. trachomatis may also manipulate the eukaryotic cell cycle. We further demonstrate that C. trachomatis infection destabilizes specific cell cycle proteins involved in the G 2 /M transition. C. trachomatis-infected cells, compared to uninfected cells, have lower levels of cyclin-dependent kinase 1. Additionally, C. trachomatis infection induces an N-terminal truncation of the mitotic cyclin B1. Manipulation of the host cell cycle may represent a strategy used by C. trachomatis to ensure a stable environment conducive to bacterial growth and replication.

show abstract

Chlamydia pneumoniae Stimulates Proliferation of Vascular Smooth Muscle Cells Through Induction of Endogenous Heat Shock Protein 60

Cited by 70 publications

References 59 publications

Development of a novel rationally designed antibiotic to inhibit a nontraditional bacterial target

Development of a novel rationally designed antibiotic to inhibit a nontraditional bacterial target

Heat Shock Protein-60 and Risk for Cardiovascular Disease

Chlamydia trachomatis Infection Induces Cleavage of the Mitotic Cyclin B1

Contact Info

Product

Resources

About